RESEARCH TOPIC: #18 - Functional Senescence in the aging population, growth hormone (GH) secretion and nutrition are compromised. GH is an essential hormone that regulates nearly every tissue in the body. Aging associated declines in GH secretion and nutrition may contribute significantly to reductions in overall physical and mental function and ability to tolerate stress insults. Our long-term goal is to identify new clinical approaches that avert deterioration in GH iecretion and nutritional intake in aging humans. Emerging evidence supports the hypothesis that pituitary GH secretion is regulated not only by GH releasing hormone (GHRH) from the hypothalamus, but also by ghrelin from the stomach. Ghrelin is a new stomach hormone that stimulates GH secretion, food intake, adiposity and weight gain. Our long-term, working hypotheses are that stomach ghrelin is a key player in linking the gastrointestinal system, i.e., nutritional intake with regulation of GH secretion, maintenance of body weight and growth, and that the stomach ghrelin-pituitary GH axis is compromised by the aging process. For this proposal, our hypothesis is that regulation of stomach ghrelin production and secretion by the intestinal hormone cholecystokinin (CCK) and pancreatic glucagon is altered by the aging process. Preliminary findings implicate a stomach-ghrelin pituitary GH axis that is influenced by dietary intake and the gut-pancreatic hormones, CCK and glucagon. Our Specific Aims are: Aim 1. To test the hypothesis that the ging process alters the regulation of pituitary GH secretion by ghrelin. Aim 2. To test the hypothesis that ging associated elevations in stomach ghrelin homeostasis are activated mechanistically by alterations in regulation by glucagon and cholecystokinin (CCK). This research is significant because we will identify mechanisms underlying regulation of GH secretion by omach ghrelin and the role of nutrition and nutritionally activated hormones in the regulation of GH secretion. This research will open up new therapeutic strategies for treatment of diseases of aging in which weight loss or gain plays a critical role. This is a compelling reason to define nutritional regulation of ghrelin and its role ingulation of GH secretion, weight gain and growth.